Necrotizing Soft Tissue Infection Staphylococcus aureus but not S. pyogenes Isolates Display High Rates of Internalization and Cytotoxicity Toward Human Myoblasts

, , , , , , , Stephanie Duguez, , , , , ,

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Necrotizing soft tissue infections (NSTIs) caused by group A Streptococcus (GAS) and occasionally by Staphylococcus aureus (SA) frequently involve the deep fascia and often lead to muscle necrosis. METHODS: To assess the pathogenicity of GAS and S. aureus for muscles in comparison to keratinocytes, adhesion and invasion of NSTI-GAS and NSTI-SA isolates were assessed in these cells. Bloodstream infections (BSI-SA) and noninvasive coagulase-negative staphylococci (CNS) isolates were used as controls. RESULTS: NSTI-SA and BSI-SA exhibited stronger internalization into human keratinocytes and myoblasts than NSTI-GAS or CNS. S. aureus internalization reached over 30% in human myoblasts due to a higher percentage of infected myoblasts (>11%) as compared to keratinocytes (<3%). Higher cytotoxicity for myoblasts of NSTI-SA as compared to BSI-SA was attributed to higher levels of psmα and RNAIII transcripts in NSTI-SA. However, the 2 groups were not discriminated at the genomic level. The cellular basis of high internalization rate in myoblasts was attributed to higher expression of α5β1 integrin in myoblasts. Major contribution of FnbpAB-integrin α5β1 pathway to internalization was confirmed by isogenic mutants. CONCLUSIONS: Our findings suggest a factor in NSTI-SA severity is the strong invasiveness of S. aureus in muscle cells, a property not shared by NSTI-GAS isolates.

Original languageEnglish
Pages (from-to)710-719
Number of pages10
JournalJournal of Infectious Diseases
Volume220
Issue number4
Early online date19 Apr 2019
DOIs
Publication statusPublished - 15 Aug 2019

Keywords

  • Staphylococcus aureus
  • Streptococcus pyogenes
  • muscle cells
  • necrotizing soft tissue infections

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    CIRI, Centre International de Recherche en Infectiologie, Université de Lyon; Inserm U1111; Ecole Normale Supérieure de Lyon; Université Lyon ; CNRS, UMR; Hospices Civils de Lyon ; Lyon, France., CIRI, Centre International de Recherche en Infectiologie, Université de Lyon; Inserm U1111; Ecole Normale Supérieure de Lyon; Université Lyon ; CNRS, UMR; Hospices Civils de Lyon ; Lyon, France., CIRI, Centre International de Recherche en Infectiologie, Université de Lyon; Inserm U1111; Ecole Normale Supérieure de Lyon; Université Lyon ; CNRS, UMR; Hospices Civils de Lyon ; Lyon, France. Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France., NeuroMyoGene Institute, Université de Lyon, CNRS UMR5310, INSERM, Lyon, France., Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France., Helmholtz-Zentrum für Infektionsforschung GmbH | Inhoffenstraße | Braunschweig, CIRI, Centre International de Recherche en Infectiologie, Université de Lyon; Inserm U1111; Ecole Normale Supérieure de Lyon; Université Lyon ; CNRS, UMR; Hospices Civils de Lyon ; Lyon, France., Duguez, S., CIRI, Centre International de Recherche en Infectiologie, Université de Lyon; Inserm U1111; Ecole Normale Supérieure de Lyon; Université Lyon ; CNRS, UMR; Hospices Civils de Lyon ; Lyon, France., Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, California, USA., Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital | Alfred Nobels Allé | Huddinge, Sweden, CIRI, Centre International de Recherche en Infectiologie, Université de Lyon; Inserm U1111; Ecole Normale Supérieure de Lyon; Université Lyon ; CNRS, UMR; Hospices Civils de Lyon ; Lyon, France., CIRI, Centre International de Recherche en Infectiologie, Université de Lyon; Inserm U1111; Ecole Normale Supérieure de Lyon; Université Lyon ; CNRS, UMR; Hospices Civils de Lyon ; Lyon, France. (2019). Necrotizing Soft Tissue Infection Staphylococcus aureus but not S. pyogenes Isolates Display High Rates of Internalization and Cytotoxicity Toward Human Myoblasts. Journal of Infectious Diseases, 220(4), 710-719. https://doi.org/10.1093/infdis/jiz167